Ellis:Research

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(Current Projects)
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'''Investigating device-chassis interactions'''<br>
'''Investigating device-chassis interactions'''<br>
Project Type: ''Foundational''<br>
Project Type: ''Foundational''<br>
-
Project Members: ''Rhys Algar, Hung Hsu''<br>
+
Project Members: ''Rhys Algar, Wei Pan''<br>
-
Collaborators: ''Guy-Bart Stan''<br>
+
Collaborators: ''Guy-Bart Stan, Microsoft''<br>
-
Most gene devices demonstrated in synthetic biology have been high-expression strength regulatory networks hosted on mid-to-high copy number plasmids in ''E.coli''. Despite being relatively simple and small, these devices are thought to be close to the maximum tolerated by the host cell - if they were any larger they would impinge on the host cell's own mechanisms. In this project, we are trying to quantify the threshold for gene device cloning into the ''E.coli'' chassis by examining a standard synthetic feed-forward loop motif expressed at a variety of different strengths in plasmid systems of varying copy number. The intention is to define a quantitative standard for inserting gene devices into chassis cells and build a predictive model to aid future design.
+
Most gene devices demonstrated in synthetic biology have been high-expression strength regulatory networks hosted on mid-to-high copy number plasmids in ''E.coli''. Despite being relatively simple and small, these devices are thought to be close to the maximum tolerated by the host cell - if they were any larger they would impinge on the host cell's own mechanisms. In this project, we are trying to quantify the threshold for gene device cloning into the ''E.coli'' chassis by examining a standard synthetic networks expressed at a variety of different strengths in plasmid systems of varying copy number. The intention is to define a quantitative standard for inserting gene devices into chassis cells and build a predictive model to aid future design.
-
'''Combinatorial modular assembly of diverse Carotenoid production pathways in yeast'''<br>
+
'''Combinatorial modular assembly of gene networks and pathways'''<br>
Project Type: ''Foundational'' and ''Applied''<br>
Project Type: ''Foundational'' and ''Applied''<br>
Project Members: ''Arturo Casini''<br>
Project Members: ''Arturo Casini''<br>
Collaborators: ''Geoff Baldwin''<br>
Collaborators: ''Geoff Baldwin''<br>
-
The availability of gene synthesis is increasing rapidly, yet there is no straightforward lab-bench method to arrange modular gene units into larger assemblies with pre-defined positions. In this project we will demonstrate a new method to rapidly assemble gene units in a pre-defined order and showcase the technique to combinatorially assemble diverse synthesis pathways in yeast. The modular gene units from the carotenoid pathways are driven by regulated promoters from a pre-existing library, and combinatorial assembly with these will produce pathways with a variety of metabolic fluxes. As well as demonstrating a rapid new assembly technique, the project will yield synthetic yeasts with high production of high-value carotenoid molecules.
+
The availability of gene synthesis is increasing rapidly, yet there is no straightforward lab-bench method to arrange modular gene units into larger assemblies with pre-defined positions. In this project we will demonstrate a new method to rapidly assemble gene units in a pre-defined order and showcase the technique to combinatorially assemble diverse synthesis pathways and gene regulatory networks using standardized parts. As well as demonstrating a rapid new assembly technique, the project will yield synthetic cells with high production of high-value therapeutic molecules.
-
'''Bottom-up design of orthogonal ''E.coli'' promoters'''<br>
+
'''Standards and parts for synthetic biology'''<br>
Project Type: ''Foundational''<br>
Project Type: ''Foundational''<br>
-
Project Members: ''Fabio Chizzolini''<br>
+
Project Members: ''Ben Blount, Tim Weenink, Serge Vasylechko, Georgios Pothoulakis''<br>
-
Synthetic biology has made great advances in its first decade but the complexity of devices has not exploded exponentially as expected. One of the major reasons for this is the lack of different parts, and specifically a dearth of regulated promoters is holding synthetic biology back. In ''E.coli'' our understanding of these promoters is advancing fast enough to consider building them up from scratch, but where do we start? In this project we will evolve a new ''orthogonal'' promoter system that uses a mutated Sigma Factor and mutated core promoter DNA sequence, so that these designer promoters are only recognised by the designer sigma factor under our control. This will lay the foundation for building a whole set of 'synthetic biology ONLY' promoters and devices that can sit in cells and yet only have limited interaction with the host cell systems.
+
-
 
+
-
'''New standards for BIOFAB projects'''<br>
+
-
Project Type: ''Foundational''<br>
+
-
Project Members: ''Ben Blount, Serge Vasylechko, Riham Satti''<br>
+
Collaborators: ''Richard Kitney, BIOFAB USA''<br>
Collaborators: ''Richard Kitney, BIOFAB USA''<br>
-
Synthetic biology requires professional characterisation of standardised parts to enable predictable and scalable construction of complex and robust devices and systems. To characterise biological parts it is useful to have a reference standard part to which it can be compared. This has been demonstrated by Kelly ''et al.'' for housekeeping promoters in ''E.coli''. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing two new standards for part characterisation: (1) a standard reference promoter for yeast selected from systems biology screening, and (2) an ultra-efficient GFP coding region with various degradation tags for dynamical characterisation at low copy numbers.
+
Synthetic biology requires professional characterisation of standardised parts to enable predictable and scalable construction of complex and robust devices and systems. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing new standards for part characterisation in E.coli and yeast, and new part libraries for engineering synthetic yeast.
 +
 
 +
'''Engineering thermophilic synthetic biology'''<br>
 +
Project Type: ''Foundational''and ''Applied''<br>
 +
Project Members: ''Elena Martinez-Klimova, Ben Reeve''<br>
 +
Collaborators: ''David Leak, TMO Renewables''<br>
 +
Engineering new function into well-characterised cells is one of the major goals of synthetic biology, but one phenotype almost impossible to add to cells like E.coli is thermostability. Instead, our lab is kick-starting synthetic biology in a Geobacillus species thermophile by developing standard measurement protocols with aerobic and anaerobic fluorescent proteins and charactersing libraries of standard, synthetic parts. We will use these to improve and diversify existing biofuel production pathways to generate high-yields and new products.
 +
 
 +
'''Parasite Protease Detection'''<br>
 +
Project Type: ''Applied''<br>
 +
Project Members: ''Nicolas Kylilis''<br>
 +
Collaborators: ''Paul Freemont, Geoff Baldwin, Bill and Melinda Gates Foundation''<br>
 +
Almost all parasites release specific proteases during their life-cycle in order to invade and ingest surrounding tissues. Rapid, cheap detection of such proteases offers a novel method for diagnosis and tracking of parasistic disease, such as Schistosoma. Following on from Imperial's 2010 iGEM team and with generous funding from the Bill and Melinda Gates Foundation, we are developing a modular whole-cell biosensor solution to detect specific proteases released by parasites.
   
   
'''Cyborg Biosensors'''<br>
'''Cyborg Biosensors'''<br>
Project Type: ''Applied''<br>
Project Type: ''Applied''<br>
-
Project Members: ''Charles Fracchia''<br>
+
Project Members: ''Piotr Faba, Charles Fracchia''<br>
-
Collaborators: ''IBM''<br>
+
Collaborators: ''Tony Cass, IBM''<br>
A single ''E.coli'' cell can sense subtle changes in its environment such as the presence of pollutants or rare metals, however it takes millions of ''E.coli'', all producing fluorophores or dyes to relay this message back to a human eye. To tackle this scale-barrier between the microbe world and human world we're developing a simple genetic part that gives an output that can be recorded by cheap nanotechnology detectors. A cyborg scheme interfacing disposable electronics with re-programmable microbes will offer low-cost, high-sensitivity environmental sensing solutions.
A single ''E.coli'' cell can sense subtle changes in its environment such as the presence of pollutants or rare metals, however it takes millions of ''E.coli'', all producing fluorophores or dyes to relay this message back to a human eye. To tackle this scale-barrier between the microbe world and human world we're developing a simple genetic part that gives an output that can be recorded by cheap nanotechnology detectors. A cyborg scheme interfacing disposable electronics with re-programmable microbes will offer low-cost, high-sensitivity environmental sensing solutions.
-
'''Degrade-and-Fire Oscillations at the Nucleus'''<br>
+
'''Bottom-up design of orthogonal ''E.coli'' promoters'''<br>
Project Type: ''Foundational''<br>
Project Type: ''Foundational''<br>
-
Project Members: ''Tim Weenink''<br>
+
Project Members: ''Fabio Chizzolini, Anna Kress''<br>
-
Collaborators: ''Mauricio Barahona, Andrew DeMello''<br>
+
Synthetic biology has made great advances in its first decade but the complexity of devices has not exploded exponentially as expected. One of the major reasons for this is the lack of different parts, and specifically a dearth of regulated promoters is holding synthetic biology back. In ''E.coli'' our understanding of these promoters is advancing fast enough to consider building them up from scratch, but where do we start? In this project we will evolve a new ''orthogonal'' promoter system that uses a mutated Sigma Factor and mutated core promoter DNA sequence, so that these designer promoters are only recognised by the designer sigma factor under our control. This will lay the foundation for building a whole set of 'synthetic biology ONLY' promoters and devices that can sit in cells and yet only have limited interaction with the host cell systems.
-
Yeast, like all eukaryotic cells, spatially separates its DNA from its protein synthesis machinery. The spatial separation offers a time-delay window where transcription factors are synthesised in the cytosol but take time to translocate to through the nuclear envelope to their site of action. In this project we are exploiting this phenomenon to produce a simple degrade-and-fire oscillator system where oscillations are determined by nuclear transport efficiency and protein degradation speeds. We intend to model our system and use microfluidics to characterise individual cells in phase.
+

Revision as of 05:30, 19 December 2011

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Latest Update: June 2011


Research in the Ellis Lab focuses on advancing biotechnology through the use of synthetic biology. Projects fall into one of two categories or belong in both:


  • 1. Foundational Synthetic Biology

Developing the tools for rapid, predictable engineering of biological devices and systems.

Examples: biopart design, assembly techniques and device synthesis, part and device characterisation, standardisation, chassis systems, mathematical models, design simulations


  • 2. Applied Synthetic Biology

Using the synthetic biology approach in biotechnology applications .

Examples: combinatorial synthesis of pathways, modular design of biosensors, cheap inducer systems for biosynthesis


Current Projects

Investigating device-chassis interactions
Project Type: Foundational
Project Members: Rhys Algar, Wei Pan
Collaborators: Guy-Bart Stan, Microsoft
Most gene devices demonstrated in synthetic biology have been high-expression strength regulatory networks hosted on mid-to-high copy number plasmids in E.coli. Despite being relatively simple and small, these devices are thought to be close to the maximum tolerated by the host cell - if they were any larger they would impinge on the host cell's own mechanisms. In this project, we are trying to quantify the threshold for gene device cloning into the E.coli chassis by examining a standard synthetic networks expressed at a variety of different strengths in plasmid systems of varying copy number. The intention is to define a quantitative standard for inserting gene devices into chassis cells and build a predictive model to aid future design.

Combinatorial modular assembly of gene networks and pathways
Project Type: Foundational and Applied
Project Members: Arturo Casini
Collaborators: Geoff Baldwin
The availability of gene synthesis is increasing rapidly, yet there is no straightforward lab-bench method to arrange modular gene units into larger assemblies with pre-defined positions. In this project we will demonstrate a new method to rapidly assemble gene units in a pre-defined order and showcase the technique to combinatorially assemble diverse synthesis pathways and gene regulatory networks using standardized parts. As well as demonstrating a rapid new assembly technique, the project will yield synthetic cells with high production of high-value therapeutic molecules.

Standards and parts for synthetic biology
Project Type: Foundational
Project Members: Ben Blount, Tim Weenink, Serge Vasylechko, Georgios Pothoulakis
Collaborators: Richard Kitney, BIOFAB USA
Synthetic biology requires professional characterisation of standardised parts to enable predictable and scalable construction of complex and robust devices and systems. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing new standards for part characterisation in E.coli and yeast, and new part libraries for engineering synthetic yeast.

Engineering thermophilic synthetic biology
Project Type: Foundationaland Applied
Project Members: Elena Martinez-Klimova, Ben Reeve
Collaborators: David Leak, TMO Renewables
Engineering new function into well-characterised cells is one of the major goals of synthetic biology, but one phenotype almost impossible to add to cells like E.coli is thermostability. Instead, our lab is kick-starting synthetic biology in a Geobacillus species thermophile by developing standard measurement protocols with aerobic and anaerobic fluorescent proteins and charactersing libraries of standard, synthetic parts. We will use these to improve and diversify existing biofuel production pathways to generate high-yields and new products.

Parasite Protease Detection
Project Type: Applied
Project Members: Nicolas Kylilis
Collaborators: Paul Freemont, Geoff Baldwin, Bill and Melinda Gates Foundation
Almost all parasites release specific proteases during their life-cycle in order to invade and ingest surrounding tissues. Rapid, cheap detection of such proteases offers a novel method for diagnosis and tracking of parasistic disease, such as Schistosoma. Following on from Imperial's 2010 iGEM team and with generous funding from the Bill and Melinda Gates Foundation, we are developing a modular whole-cell biosensor solution to detect specific proteases released by parasites.

Cyborg Biosensors
Project Type: Applied
Project Members: Piotr Faba, Charles Fracchia
Collaborators: Tony Cass, IBM
A single E.coli cell can sense subtle changes in its environment such as the presence of pollutants or rare metals, however it takes millions of E.coli, all producing fluorophores or dyes to relay this message back to a human eye. To tackle this scale-barrier between the microbe world and human world we're developing a simple genetic part that gives an output that can be recorded by cheap nanotechnology detectors. A cyborg scheme interfacing disposable electronics with re-programmable microbes will offer low-cost, high-sensitivity environmental sensing solutions.

Bottom-up design of orthogonal E.coli promoters
Project Type: Foundational
Project Members: Fabio Chizzolini, Anna Kress
Synthetic biology has made great advances in its first decade but the complexity of devices has not exploded exponentially as expected. One of the major reasons for this is the lack of different parts, and specifically a dearth of regulated promoters is holding synthetic biology back. In E.coli our understanding of these promoters is advancing fast enough to consider building them up from scratch, but where do we start? In this project we will evolve a new orthogonal promoter system that uses a mutated Sigma Factor and mutated core promoter DNA sequence, so that these designer promoters are only recognised by the designer sigma factor under our control. This will lay the foundation for building a whole set of 'synthetic biology ONLY' promoters and devices that can sit in cells and yet only have limited interaction with the host cell systems.

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